J Math Chem (2010) 48:179–186

DOI 10.1007/s10910-009-9659-5

ORIGINAL PAPER

Mathematical modelling of enzyme kinetics reaction

mechanisms and analytical solutions of non-linear
reaction equations

A. Meena · A. Eswari · L. Rajendran

Received: 3 June 2009 / Accepted: 26 December 2009 / Published online: 9 January 2010
© Springer Science+Business Media, LLC 2010

Abstract The boundary value problem in basic enzyme reactions is formulated and
approximate expressions for substrate and product concentrations are presented. He’s
variational iteration method is used to give approximate and analytical solutions of
non-linear reaction equations containing a non-linear term related to enzymatic reac-
tion. The relevant analytical solutions for the substrate, enzyme, substrate-enzyme
and product concentration profiles are discussed in terms of dimensionless reaction
diffusion parameters K , λ and ε.

Keywords Enzyme kinetics · Non-linear reaction equations · Variational iteration

method · Michaelis–Menten kinetics

1 Introduction

The vast majority of chemical transformations inside cells are carried out by proteins
called enzymes. Enzymes accelerate the rate of chemical reactions (both forward and
backward) without being consumed in the process and tend to be very selective, with
a particular enzyme accelerating only a specific reaction. Enzymes are important in
regulating biological processes, for example, as activators or inhibitors in a reaction.
To understand the role of enzyme kinetics, the researcher has to study the rates of
reactions, the temporal behaviours of the various reactants and the conditions which
influence the enzyme kinetics. Introduction with a mathematical bent is given in the
books by Rubinow [1], Murray [2], Segel [3] and Roberts [4] . The purpose of this com-
munication is to derive asymptotic approximate expressions for the substrate, product,

A. Meena · A. Eswari · L. Rajendran (B)

Department of Mathematics, The Madura College (Autonomous), Madurai 625011, Tamilnadu, India
e-mail: [email protected]; [email protected]

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enzyme and enzyme-substrate concentrations using variational iteration method for

all values of dimensionless reaction diffusion parameters K , λ and ε.

2 Mathematical formulation and solution of the problem

The enzyme kinetics in biochemical systems have traditionally been modelled by

ordinary differential equations which are based solely on reactions without spatial
dependence of the various concentrations. The model for an enzyme action, first elu-
cidated by Michaelis and Menten suggested the binding of free enzyme to the reac-
tant forming an enzyme-reactant complex. This complex undergoes a transformation,
releasing the product and free enzyme. The free enzyme is then available for another
round of binding to a new reactant. Traditionally, the reactant molecule that binds to
the enzyme is termed the substrate S, and the mechanism is often written as:

k1 k2
E + S ↔ ES → E + P (1)
k−1

This mechanism illustrates the binding of substrate S and release of product P. E

is the free enzyme and ES is the enzyme-substrate complex. k1 , k−1 and k2 denote the
rates of reaction of these three processes. Note that substrate binding is reversible but
product release is not. The concentration of the reactants in the Eq. (1) is denoted by
lower case letters

s = [S], e = [E], c = [S E], p = [P] (2)

The law of mass action leads to the system of following non-linear reaction equa-
tions [2]

ds
= −k1 es + k−1 c (3a)
dt
de
= −k1 es + (k−1 + k2 )c (3b)
dt
dc
= k1 es − (k−1 + k2 )c (3c)
dt
dp
= k2 c (3d)
dt

where k1 is the forward rate of ES complex formation and k−1 is the backward rate
constant. The boundary conditions are

s(0) = s0 , e(0) = e0 , c(0) = 0, p(0) = 0. (4)

Adding equations (3b) and (3c), we get,

de/dt + dc/dt = 0 (5)

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Using the initial conditions (4) we obtain

e(t) + c(t) = e0 (6)

with this, the system of ordinary differential equations reduce to only two, for s and
c, namely

ds
= −k1 e0 s + (k1 s + k−1 )c, (7)
dt
dc
= k1 e0 s − (k1 s + k−1 + k2 )c, (8)
dt
with initial conditions s(0) = s0 , c(0) = 0. By introducing the following parameters

k1 e0 t s(t) c(t) p(t)

τ = , u(τ ) = , v(τ ) = , w(τ ) =
ε s0 e0 e0
k2 k−1 + k2 e0
λ= , k= , ε= (9)
k 1 s0 k 1 s0 s0

the system of Eqs. (7) and (8) and the initial conditions [Eqs. (4)] can be represented
in dimensionless form as follows:
du
= −uε + ε(u + k − λ)v, (10a)
dτ
dv
= u − (u + k)v (10b)
dτ
dw
= λv (10c)
dτ
u(0) = 1, v(0) = 0, w(0) = 0 (11)

The above system of non-linear equations can be solved analytically in a simple and
closed form using variational iteration method [5–10] (Ref Appendix A). The solutions
of the above Eqs. 10a and 10b become

e−ετ  −kτ 2
u(τ ) = e−ετ − e ε − kε{ε(λ − k)τ + e−ετ + e−kτ }
k(k − ε)2
+ k{ke−ετ + ε(λ − k)kτ + ε(λ − k)e(ε−k)τ } − (ε − k)2

− ε(λ − k)k (12)
 
e−ετ − e−kτ e−kτ (e−kτ − 1) (e(k−2ε)τ − 1)
v(τ ) = − + (13)
k−ε k−ε ε k − 2ε

Equations (12) and (13) represent the analytical expressions of the substrate u(τ )
and enzyme-substrate v(τ ) concentration. From the Eq. (6), we can also obtain the
dimensionless concentration of enzyme

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E(τ ) = e(t)/e0 = 1 − v(τ ) (14)

Equation (3d) is uncoupled with the first three equations. The dimensionless concen-
tration of the product is given by

τ
w(τ ) = λ v(t  )dt 
0
 −kτ  −2ετ
λ e − 1 1 − e−ετ e−2kτ (1 − 2ekτ )+1 1 e −1
= + + +
k−ε k ε 2kε k − 2ε 2ε

1 − e−kτ
+ (15)
k

Equations (14) and (15) represent the new analytical expressions of the concentrations
of enzyme E(τ ) and product w(τ ) for all values of parameters k, λ and ε

3 Discussion

Figures 1, 2, 3 and 4 show the analytical expressions of concentrations of substrate

u, enzyme E, enzyme-substrate complex v and product w for various values of dimen-
sionless reaction parameters k, λ and ε. From these figures, it is inferred that the value
of the concentration of substrate decreases gradually from its initial value of the con-
centration (u(0) = 1). The concentration of substrate becomes zero when τ ≥ 4. (see

Fig. 1 Profile of the normalized concentrations of the substrate u, enzyme-substrate complex v, enzyme E
and product w for k = 1, ε = 0.6, and λ = 0.5. The curves are plotted using Eqs. (12)–(15)

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Fig. 2 Profile of the normalized concentrations of the substrate u, enzyme-substrate complex v, enzyme E
and product w for k = 2, ε = 0.5, and λ = 1. The curves are plotted using Eqs. (12)–(15)

Fig. 3 Profile of the normalized concentrations of the substrate u, enzyme-substrate complex v, enzyme E
and product w for k = 5, ε = 0.8 and λ = 3. The curves are plotted using Eqs. (12)–(15)

left hand side of Figs. 1 and 2). The concentration of the product increases slowly
from the initial concentration (w(0) = 0). The concentration of the product reaches
the constant value when τ ≥ 6 for all values of reaction parameters. Also when the
value of the parameters k, λ and ε increases, the value of the product decreases. When
0.2 ≤ τ ≤ 0.5, enzyme reaches the minimum value and enzyme- substrate reaches

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Fig. 4 Profile of the normalized concentrations of the substrate u, enzyme-substrate complex v, enzyme E
and product w for k = 10, ε = 1 and λ = 5. The curves are plotted using Eqs. (12)–(15)

the maximum value. Concentrations of enzyme- substrate and substrate reach zero
value when τ ≥ 5 for all values of reaction parameters. The concentration of substrate
u reaches the steady-state value (u = 0) when τ ≥ 3.

4 Conclusion

Approximate analytical solutions to the non-linear reaction equations are presented

using variational iteration method. A simple, straight forward and a new method of
estimating the concentrations of substrate, product, enzyme-substrate complex and
enzyme are derived. This solution procedure can be easily extended to all kinds of
system of coupled non-linear equations with various complex boundary conditions in
enzyme-substrate reaction diffusion processes [11].

Acknowledgments This work was supported by the Department of Science and Technology (DST)
Government of India. The authors also thank Mr. M.S. Meenakshisundaram, Secretary, The Madura College
Board Dr. T.V. Krishnamoorthy, Principal, and S.Thiagarajan Head of the Department of Mathematics, The
Madura College, Madurai, for their constant encouragement. It is our pleasure to thank the referees for their
valuable comments.

Appendix A

In this appendix, we derive the general solution of non-linear reaction Eq. (10) using
He’s variational iteration method. To illustrate the basic concepts of variational itera-
tion method (VIM), we consider the following non-linear partial differential equation
[6–10]

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J Math Chem (2010) 48:179–186 185

L[u(x)] + N [u(x)] = g(x) (A1)

where L is a linear operator, N is a nonlinear operator, and g(x) is a given continuous

function. According to the variational iteration method, we can construct a correct
functional as follows [9]

x
 
u n+1 (x) = u n (x) + λ L[u n (τ )] + N [ũ n (τ )] − g(τ ) dτ (A2)
0

where λ is a general Lagrange multiplier which can be identified optimally via varia-
tional theory, u n is the nth approximate solution, and ũ n denotes a restricted variation,
i.e., δ ũ n = 0. In this method, a trail function (an initial solution) is chosen which
satisfies given boundary conditions. Using above variation iteration method we can
write the correction functional of Eq. (10) as follows

u n+1 (τ ) = u n (τ )
⎡ ∼ ∼ ∼
⎤
x         
+ λ1 ⎣u n (ξ ) + εu n (ξ ) − εk vn (ξ ) +ελ vn (ξ ) − εu n (ξ )vn (ξ )⎦ dξ
0
(A3)
⎡ ∼ ∼
⎤
x      
vn+1 (τ ) = vn (τ ) + λ2 ⎣vn (ξ ) − u n (ξ ) +kvn (ξ ) + u n (ξ )vn (ξ )⎦dξ (A4)
0

Taking variation with respect to the independent variable u n and vn , we get

δu n+1 (τ ) = δu n (τ )
⎡ ∼ ∼ ∼
⎤
x         
+ δ λ1 ⎣u n (ξ ) + εu n (ξ ) − εk vn (ξ ) +ελ vn (ξ ) − εu n (ξ )vn (ξ )⎦ dξ
0
(A5)
⎡ ∼ ∼
⎤
x      
δvn+1 (τ ) = δvn (τ ) + δ λ2 ⎣vn (ξ ) − u n (ξ ) +kvn (ξ ) + u n (ξ )vn (ξ )⎦dξ
0
(A6)

where λ1 and λ2 are general Lagrangian multipliers, u 0 and v0 are initial approx-
∼ ∼ ∼
        
imations or trial functions, u n (ξ ), ε(λ − k)vn (ξ ) and u n (ξ )vn (ξ ) are considered as
restricted variations i.e δ ũ n = 0, δ ṽn = 0 and δ ũ n ṽn = 0. Making the above correc-
tion functional (A5) and (A6) stationary, noticing that δu n (0) = 0, δvn (0) = 0 and
δu n (0)vn (0) = 0.

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δu n : 1 + λ1 (ξ )|ξ =τ = 0, δvn : 1 + λ2 (ξ )|ξ =τ = 0 (A7)

 
δu n : −λ1 (ξ ) + ελ(ξ )ξ =τ , δvn : −λ2 (ξ ) + kλ(ξ )ξ =ξ = 0 (A8)

The above equations are called Lagrange-Euler equations. The Lagrange multipliers,
can be identified as

λ1 (ξ ) = −eε(ξ −τ )
(A9)
λ2 (ξ ) = −ek(ξ −τ )

substituting the Lagrangian multipliers and n = 0 in the iteration formula [Eqs. (A3)
and (A4)] we obtain,

τ

u 1 (x) = u 0 (x) − eε(ξ −τ ) u 0 (ξ ) + εu 0 (ξ ) − εu 0 (ξ )v0 (ξ ) − εkv0 (ξ )
0

+ελv0 (ξ ) dξ (A10)
 τ
 
v1 (x) = v0 (x) − ek(ξ −τ ) v0 (ξ ) − u 0 (ξ ) + u 0 (ξ )v0 (ξ ) + kv0 (ξ ) dξ
0
(A11)

Assuming that its initial approximate solution which satisfies the boundary condi-
tion (11) have the form

u 0 (x) = e−ετ
v0 (x) = (e−ετ − e−kτ )/(k − ε) (A12)

By the iteration formula (A10) and (A11) we have the Eqs. (12) and (13) in the text.

References

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2. J.D. Murray, Mathematical Biology (Springer, Berlin, 1989), p. 109
3. L.A. Segel, Mathematical Models in Molecular and Cellular Biology (Cambridge University
Press, Cambridge, 1980)
4. D.V. Roberts, Enzyme Kinetics (Cambridge University Press, Cambridge, 1977)
5. J.H. He, J. Comput. Appl. Math. 207, 3 (2007)
6. J.H. He, Int. J. Nonlinear Mech. 34(4), 699 (1999)
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